An investigation of the synthesis of vilazodone

Abstract

A novel synthetic route toward vilazodone is described by using 4-cyanoaniline and 5-bromo-2-hydroxybenzaldehyde as starting materials, with an overall yield of 24% and 99% purity. First, the intermediate (3-(4-chlorobutyl)-1 H-indole-5-carbonitrile) is synthesized via diazotization of 4-cyanoaniline, followed by Fischer indole cyclization with 6-chlorohexanal. Subsequently, another intermediate, 5-(piperazin-1-yl)benzofuran-2-carboxamide, is generated via aromatic nucleophilic substitution of 5-bromobenzofuran-2-carboxamide with piperazine. Finally, vilazodone is obtained via nucleophilic substitution of the above two key intermediates by treatment with Et3N/K2CO3. In comparison to the original process, this route avoids the use of expensive and toxic reagents and resolves issues such as safety, environmental concerns, and high costs.